Predicting protein functions through non-negative matrix factorization regularized by protein-protein interaction network and gene functional information

Protein function prediction is necessary for understanding life and is valuable for application on drug design and health care. It is still a big challenge to predict protein function correctly by integrating multi-biological information. In this work, we propose a novel non-Negative Matrix Factorization (NMF) based method regularized by PPI network and GO similarity network, namely PONMF, for protein function prediction, which decomposes the known GO-protein association matrix into two low-rank matrixes for proteins and GO terms. In the course of factorization, PONMF incorporates the label matrix factorization term, an additional network regularization term and a GO similarity regularization term into the objective function. Finally, the potential protein functions are predicted by referring to the product of the two low-rank matrixes. PONMF not only successfully integrates diverse biological information to predict protein functions, but also naturally partitions proteins into different modules and infers functions from the proteins in the same modules. Our methods as well as the other two state-of-the-art methods (UBiRW and NMFGO) are applied to predict functions for protein of S. cerevisiae and H. sapiens. The prediction results show that PONMF outperforms the other two existing methods.